Critical Assessment of Nucleic Acid Electrostatics via Experimental and Computational Investigation of an Unfolded State Ensemble

Link: http://pubs.acs.org/cgi-bin/abstract.cgi/jacsat/asap/abs/ja800854u.html

Electrostatic forces, acting between helices and modulated by the
presence of the ion atmosphere, are key determinants in the energetic
balance that governs RNA folding. Previous studies have employed
Poisson−Boltzmann (PB) theory to compute the energetic contribution of
these forces in RNA folding. However, the complex interaction of these
electrostatic forces with RNA features such as tertiary contact
formation, specific ion-binding, and complex interhelical junctions
present in prior studies precluded a rigorous evaluation of PB theory,
especially in physiologically important Mg2+ solutions. To critically
assess PB theory, we developed a model system that isolates these
electrostatic forces. The model system, composed of two DNA duplexes
tethered by a polyethylene glycol junction, is an analog for the
unfolded state of canonical helix-junction-helix motifs found in
virtually all structured RNAs. This model system lacks the
complicating features that have precluded a critical assessment of PB
in prior studies, ensuring that interhelical electrostatic forces
dominate the behavior of the system. The system's simplicity allows PB
predictions to be directly compared with small-angle X-ray scattering
experiments over a range of monovalent and divalent ion
concentrations. These comparisons indicate that PB is a reasonable
description of the underlying electrostatic energies for monovalent
ions, but large deviations are observed for divalent ions. The
validation of PB for monovalent solutions allows analysis of the
change in the conformational ensemble of this simple motif as salt
concentration is changed. Addition of ions allows the motif to sample
more compact microstates, increasing its conformational entropy. The
increase of conformational entropy presents an additional barrier to
folding by stabilizing the unfolded state. Neglecting this effect will
adversely impact the accuracy of folding analyses and models.

Various Tuolumne Trips

Been busy travelling around random parts of the west coast + desert
southwest. Here are a selection of pictures from various trips this
summer:

July 4 - 5: OZ (5.10d), Gram Traverse (5.10d), Hobbit Book (5.7R), Crying Time Again (5.10aR), Western Front TR'ing, West Country (5.7)

- Cory led most of the hard pitches since he was the designated rope
gun for the weekend. I sitll wanted to pull my own weight, so I led
the 5.10b corner pitch on OZ -- truly a classic pitch! Took a 15-foot
fall on the Gram Traverse while following when my foot skated and I
blew a cam. We simulclimbed the first two pitches of Hobbit Book.

- Led the 5.9 pitch on Crying Time Again while Cory led the crux
pitches. Afterwards, did a lot of slab practice on TR at the Western
Front (DAFF Dome). Cruised up West Country with Kim. It was my third
time up West Country and this climb never fails to deliver. I remember
being very scared on the second pitch; West Country was my second
Tuolumne Lead, and probably my 4th trad lead ever! Now it's a piece of
cake ..

- Justin and his brother stopped by on their way out of the meadows
after seeing our car parked by Tenaya. We caravaned to Groveland where
we finished up the weekend at the Cocina Michoacana -- great Mexican!

July 19 - 20: Crying Time Again (5.10aR), Northwest Books (5.9 variation), Bouldering at Tenaya Lake (stormed out of the meadows)

- After doing it once, I decided I really wanted to lead the crux
pitches of Crying Time Again (exposed and steep 5.10a!). So I
convinced Kim to follow me. She did an admirable job in spite of her
sprained "cankle." Her tenacity and determination got her through the
final crux moves, even though she was shaking from the effort.
Impressive!

- We had originally planned to try for the Lembert Dome trifecta:
Crying Time Again, Direct Northwest Face, Northwest Books, but Kim's
swollen ankle meant that she wouldn't be able to climb cracks very
well. So we decided to finish off the day at Northwest Books. I did
the 5.9 variation (highlighted in ANAM) and found it surprisingly
strenuous and spicy!

- After dinner and a bivy above the Mobil station, we went back to
the Meadows to try Direct NW Face. However the weather was looking
iffy and in 40 minutes it went from relatively clear, to dark and
menacing. Rain started to fall and we wisely beat a retreat back to
the car. Knowing that the day was shot, we headed to Tenaya lake for a
quick bouldering session before an early ride back to the Bay area.

July 27: West Ridge of Mt. Conness (5.6)

- Eu-jin and I have wanted to do Mt. Conness for a while but each
time we've tried, laziness intervened and we always ended up doing
someting else. This time, we made a concerted effort not to get
distracted and found ourselves waking up at 4:30am to begin the long
approach to Conness. The appraoch was deceptively long and difficult
(the summit plateau is hidden from below). However, the true
difficulty was in the dangerous scramble down from the plateau to the
base. We must have gotten off-route because we found ourselves in
extremely loose territory, we rock raining down each step we took.
Next time we'll have to find a better way.

- Climbing went fast; we simulclimbed the entire ridge on 30m of
rope, stopping only to exchange gear. Beautiful setting, with great
views of Roosevelt lake and tuolumne (unfortunately, our views were
obscured by thick smoke from a forest fire in mariposa).

- The descent was long and tiring. At altitude, I find it hard to eat
the requisite amount of calories to sustain movement and I quickly
found myself out of gas and hitting the wall. A quick break and a few
bars later, I was moving again. I must remember to eat more on these
trips! This was also the first time I had used trekking poles and
found them invaluable. I was very surprised to find that at the end of
the day, my muscles were tired, by my joints were not aching.

Picture Captions:
1 - Gearing up at the base of OZ on Drug Dome
2 - Climbing the beautiful 5.10b dihedral on OZ
3 - Following Cory on the first pitch of the Gram Traverse. This is
right before I blew a foot placement and fell, ripping out a cam which
sent me tumbling onto a #1 Camalot
4 - Simulclimbing quickly up the first two pitches of Hobbit Book
5 - Cory and I on the top of Mariolumne Dome after climbing Hobbit Book
6 - A picture of Drug Dome. OZ ascends the prominent right-facing
corner and ends under the roof. Gram Traverse traverses right, under
the roof, before escaping up.
7 - Party at the base of West Country! Kim, Eu-jin and I just before
our cruise up Stately Pleasure Dome.
8 - Kim following the first funky, greasy, and insecure pitch of West Country.
9 - View of Tenaya Lake from the top of Stately Pleasure Dome
10 - Bouldering at Tenaya lake
11 - Approaching Mt. Conness
12 - The massive Southwest Face of Mt. Conness. The West ridge ascends
the ridge above the face.
13 - On the descent from the summit plateau towards the base
14 - Goofing off somewhere on the ridge
15 - The steeper headwall of Crying Time Again looming over the first pitch

myilibrary.com: end-user restrictions gone crazy! Or: How to download entire e-books from myilibrary.com

Trip Report: Snake Dike, Half Dome + Tuolumne Meadows (June 2008)

At 5.7, Snake Dike is probably the easiest technical climbing route up
Yosemite's Half Dome. However, despite its easy grade, leaders still
face runouts of up to 40 feet, especially on the easier sections of
climbing. I've wanted to do this route for many years but hadn't found
the opportunity to do so. In May, Eu-Jin and I finally decided to
go. Because the top of Half Dome is a goal that many people in the Bay
Area would like to attempt, I invited a bunch of friends to join us.
While we climbed Snake Dike, they would reach the top of Half Dome via
the more conventional cables
route.

We left on a friday, stopping at In 'N Out for the obligatory pre-road
trip meal before stealth camping at the Rock Piles just outside of the
park. The approach hike to the base of Snake Dike is quite long; to
get an early stat, we elected for an alpine start, waking before dawn.
Eu-jin, Young, and I departed Happy Isles first, trying to get an
early start. We made good time, reaching the top of Vernal falls in
about an hour and a half where we departed the main trail, heading to
the base via the climbers trail that winds its way past Liberty Cap
and Mt. Broderick. Around Lost Lake, we sighted a juvenile bear as it
ambled lazily across the trail before dissappearing into the thick
brush. While we made very good time getting to the climber's trail,
the last hour of the approach was difficult, traversing through many
broken 4th class ledges. We reached the base at the same time as
another party; since we were climbing as a team of three, we let them
pass us since they would move faster with two people.

I was a bit worried about the first pitch given its reputation for
being slippery. To my surprise, the moves were far easier than
expected and I gained the belay without much difficulty. With the crux
pitch dispatched so quickly and easily, I relaxed and brought Eu-Jin
and Young to the belay. Young climbed very well on his first outdoor
climb, negotiating the moves without much difficulty. The rest of the
climb was a nice, low-angle romp. However, I still had to pay
attention on the later pitches --- even at 5.4, a 40-foot runout gives
you something to think about! As the angle receded, we unroped and
started hiking up the last agonizing 1000 feet of low-angle slab.

The summit was quite jarring. The last time I was here was after my
ascent of the Regular Northwest Face. At the time, a storm had chased
the hordes of tourists from the summit leaving it deserted when we
topped out. This time, the hordes of tourists were out in force; from
the crowds on the hike in, I knew they would be there, but the sheer
number of people still surprised me.

We were all very tired on the hike down (I didn't pack enough food)
and we found ourselves slowing down to a grind. However, we made it
back down to Happy Isles. We met up with our friends and ended the day
with beers and pizza at Curry Village.

Gen, Craig, Aathi, and I went back to the rock piles to sleep while
the rest of the group departed for home. We woke the next morning and
enjoyed a nice buffet breakfast in El Portal. Craig and Aathi left to
see Tuolumne while Gen and I spent the day in the Valley, cragging at
the Five and Dime cliff with Chris Chan, whom we met at the Ahwahnee
hotel. After cragging, Gen and I went to Tuolumne to see if we could
do a short backpacking trip in the high country. To our surprise, the
campgroud was closed and there was still quite a bit of snow in the
high country.

With our trip in doubt, we decided to wait until the next morning to
see what the rangers at the Wilderness center advised. We had a nice
dinner at the Tioga Pass Resort before heading down to bivy above Mono
lake. Unfortunately, our tent pole snapped resulting in a sagging,
misshapened tent. The backpacking trip was looking more and more in
doubt. The next morning, we checked with the ranger who advised us
against proceeding due to the heavy snow and high winds. We agreed and
went day-hiking instead, reaching the top of Lembert Dome and cooking
a nice lunch with the food we had bought for our backpacking trip. A
quick bouldering session at Tenaya lake ended the day before we headed
back to the Bay area.

Profligate lifestyles --- who's to blame, the lender or the borrower?

The New York Times has an article on how some have landed themselves
into staggering amounts of debt. The thing that really bothered me
about this article is that it portrays those facing bankruptcy and
financial ruin in a very sympathetic light, showing how their lives
have been ruined by predatory lending practices. The series' subtitle
is "A series about the surge in consumer debt and the lenders who made
it possible", a subtle way of shifting blame from those who willingly
spent beyond their means to those who lent them money.

In my mind, the series doesn't go far enough into the past. Why focus
on the lifestyles these Americans are about to lose; instead, focus on
the chain of crazy decisions that these people willingly made that
landed them into debt in the first place. Nobody forced them to sign
on the dotted line --- that's something that no "predatory" lender can
do. These people never could have afforded the lifestyles, the
purchases, and the homes that they borrowed to pay for --- why not
place the blame on them?

http://www.nytimes.com/2008/07/20/business/20debt.html#/from/1

Schrodinger's Cat ... Fuxkz y0u0RzZZ!

Who are y'all?

I'm trying to avoid implementing the last bit of code for my research.
So, instead, I'll post quickly to my blog with a question. Early on, a
few people I had never met subscribed to my blog. This piqued my
curiosity --- who are you, and why did you subscribe? I'm not
complaining, but I'm just curious! If you're still reading, respond
via comments ...

Marty Feldstein on Oil Prices

I stumbled upon this article today (strangely enough, in the supertopo.com forums, where more than a few economic PhD's seem to lurk). In the article, Marty Feldstein (Harvard students will recognize him as the famed Ec10 lecturer) gives a clear and concise explanation for the seemingly paradoxical rapid short-term increase in oil prices. The confusion and frustration over this topic has been palpable in recent months given the clamorous calls in Congress for increasing regulation of "oil speculators" --- easy scapegoats for politicians desperate to salve the woulds inflicted by >$4 gas. The confusion is understandable --- "If current supply and demand have remained largely stable, how can oil prices rise so quickly?"

However, Feldstein gives a simple resolution to this "violation" of the law of supply and demand. Today's oil prices are not only driven by current supply and demand, they're also driven by the future expectation of how oil prices will behave:

[T]he fundamental insight is that owners of oil will adjust their production and inventories until the price of oil is expected to rise at the rate of interest, appropriately adjusted for risk. If the price of oil is expected to rise faster, they'll keep the oil in the ground. In contrast, if the price of oil is not expected to rise as fast as the rate of interest, the owners will extract more and invest the proceeds.

Stated simply, oil producers face a choice between selling oil today, and selling oil tomorrow. If they expect the price of oil to rise quickly (driven, say, by the expected increase in demand in places like China and India), they'll just wait to sell their oil because the alternative --- selling the oil today and investing at the current risk-adjusted interest rate --- will give them less profit.

The current volatility in current prices isn't driven by fluctations in how oil is used currently; instead, it's being driven by volatility in the expectation of future prices. This makes oil fundamentally different from other commodities because it can be stored in the ground. Most agricultural commodities, unlike oil, must be consumed relatively quickly (every try and eat oranges from eight months ago?) which means their current prices more closely reflect current supply and demand realities.

For Feldstein, this quirk of oil actually presents an upside, an advantage unlike many other commodities; we can actually lower oil prices today by taking steps to ensure that future increases in oil price are low. If we can convince oil producing countries like the Saudis that oil prices will rise less quickly than they expect, they'll be inclined to sell more oil today, because they can make more money by investing the profits, rather than waiting to sell their oil. This will of course increase supply, driving prices downward.

Some of the actions we can take are pretty obvious --- increasing the minimum mileage requirements on vehicles or drilling in the Arctic National Wildlife Refuge comes to mind. However, I think Feldstein might be reaching here. China and India will still demand huge amounts of oil regardless of any change in US consumption; this huge increase in future demand may swamp out any downward pressure on current oil prices caused by policy changes announced today.

Nevertheless, despite the pain of current oil prices, it's increasingly clear that our nation's dependence on oil has national security and political consequences that extend far beyond our inalienable right to drive large and wasteful SUV's at a cheap price. Even if oil prices fall, it's important that we find a way to wean ourselves off our addiction to oil. Doing so will require political will --- let's hope our elected leaders can rise to the challenge.

http://www.nber.org/feldstein/wsj07012008.html

 

 

 

Improvements to proPosterous!

In some spare time today, I just made some changes to the look and
feel of proPosterous. A lot of what I didn't like in the first version
of proPosterous has been fixed. Hopefully you guys enjoy them!

- Posts now have dates associated with them so that people can see
how old your posts are. It's even grammatically correct!

- Javascript code was added so that you don't have to click out of
Facebook to read blogs. Instead, clicking on the 'Expand/Collapse'
will bring up your blog post right in your profile. Unfortunately,
embedded media like audio, video, and documents have to be filtered
out so they won't show up inside Facebook. However, your readers can
still click through to your blog to view this content. The filtering
process also has the occasional side effect of making weird HTML so
sometimes it doesn't render properly. I'll try and fix that whenever I
have more spare time.

- More code was added to parse embedded youtube videos from
your blog and post them into your facebook profile!

- Instead of displaying only the first 32 subscribers in your "Who's
reading" section, the script now randomly selects and displays 32 of
them.

- Meet the computer behind the magic -- he's the 6 year-old Vaio that
runs the show. Hopefully he won't crash anytime soon. His fan is
grinding away ... slooowly. =)

LN2 ice cream

Treat for a hot day --- liquid nitrogen ice cream!